A kind of preparation method of idebenone

A technology of idebenone and benzoquinone, which is applied in the field of preparation of idebenone, can solve the problems of long reaction route, low yield and high cost, and achieves the advantages of few reaction steps, easy-to-obtain raw materials and low-cost raw materials. Effect

Active Publication Date: 2020-08-04
YANGZHOU ZHONGHUI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0017] Combining the above three methods, it is found that there are disadvantages such as long reaction route, high cost of reaction reagents (Fremmell's salt, cerium ammonium nitrate, lithium aluminum hydride), low yield, etc., and are not suitable for large-scale production

Method used

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  • A kind of preparation method of idebenone
  • A kind of preparation method of idebenone
  • A kind of preparation method of idebenone

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preparation example Construction

[0033] A typical implementation of the present invention provides a preparation method of idebenone, comprising the steps of:

[0034] 1) Coenzyme Q 0 Put 11-hydroxyundecanoic acid in a ratio of 1:3 into a container with a thermometer, add copper chloride, copper sulfate, copper acetate, silver carbonate, silver oxide, palladium chloride or a metal salt of palladium acetate As a catalyst, the catalyst is added in an amount of coenzyme Q 0 0.1~2eq of molar weight;

[0035] 2) Add ethanol and water for ultrasonic dissolution, and raise the temperature to 40-90°C;

[0036] 3) Under the protection of oxygen, add oxidizing agent 30% hydrogen peroxide;

[0037] 4) Continue the heat preservation reaction for 1-4 hours, add water to quench the reaction, and the reaction system is extracted

[0038] Washing with water, drying, distillation under reduced pressure, and column chromatography to obtain crystal 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, namely idebenon...

Embodiment 1

[0054] coenzyme Q 0 preparation of

[0055] Weigh 3.6g of raw material 3,4,5-trimethoxytoluene, add 0.33ml of concentrated sulfuric acid to 10ml of ethanol solution, stir and dissolve, slowly add 4ml of oxidant peroxyacetic acid with a concentration of 10mol / L dropwise, drop within 10 minutes Complete reaction at 35°C for 2 hours, TLC point plate monitoring raw materials have been completely reacted, stop the reaction, add 20ml of water to quench the reaction, extract with dichloromethane, organic layer with 5% FeCl 3 30 mL was washed 3 times, and washed with water until the pH of the aqueous layer reached 6. Combined organic layers were dried and treated, recrystallized with petroleum ether to obtain coenzyme Q in red needle-like crystals 0 , yield 86%, melting point 55-58 ℃.

[0056] Preparation of idebenone

[0057] Weigh Coenzyme Q 0 1.2g, 1.50g of 11-hydroxyundecanoic acid, 0.2g of copper chloride catalyst, put in a 250ml three-necked round bottom flask with a th...

Embodiment 2

[0068] coenzyme Q 0 preparation of

[0069] Weigh 3.6g of the raw material 3,4,5-trimethoxytoluene, add 0.75ml of pure formic acid to 10ml of methanol solution, stir and dissolve, slowly add 10ml of oxidant cerium ammonium nitrate with a concentration of 2mol / L, and drop it within 10 minutes Complete, react at 30°C for 1.5 hours, TLC spot plate monitors that all the raw materials have reacted, stop the reaction, add 20ml of water to quench the reaction, extract with dichloromethane, and use 5% FeCl for the organic layer 3 30 mL was washed three times, and washed with water until the pH of the aqueous layer reached 5.5. Combined organic layers were dried and treated, recrystallized with petroleum ether to obtain coenzyme Q in red needle-like crystals 0 , yield 78%, melting point 55-58 ℃.

[0070] Preparation of idebenone

[0071] Weigh Coenzyme Q 0 1.2g, 1.50g of 11-hydroxyundecanoic acid, 0.1g of copper sulfate catalyst, put in a 250ml three-necked round-bottomed flas...

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Abstract

The invention relates to a preparation method of idebenone. The method comprises the following steps: adding an oxidant hydrogen peroxide to coenzyme Q0 and 11-hydroxyundecanoic acid used as raw materials and copper chloride, copper sulfate, copper acetate, silver carbonate, silver oxide, palladium chloride or palladium acetate used as a catalyst under the protection of oxygen, and carrying out a free radical alkylation reaction; and carrying out extraction, water washing, drying, reduced pressure distillation and column chromatography on the obtained reaction system to obtain a yellow needle-like crystal 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, that is idebenone. The preparation method has the advantages of simplicity in operation, low cost and high yield, and is suitable for the large-scale industrial production of idebenone.

Description

technical field [0001] The invention relates to the field of organic drug synthesis, in particular to a preparation method of idebenone. Background technique [0002] Idebenone (Idebenone, IDBN), the chemical name is 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, which is a product of Japan Takeda Pharmaceutical Co., Ltd. The drug for improving brain function developed by the company was first launched in Japan in December 1986. Idebenone can activate the function of thread-pulling body, improve brain function metabolism and brain dysfunction; it can improve the utilization rate of glucose in the brain, promote the generation of ATP, and improve the metabolism of neurotransmitter 5-hydroxytryptamine in the brain ; and has a strong antioxidant and free radical scavenging effect. It is mainly used clinically to treat many degenerative diseases of the central nervous system related to oxidative stress, such as Parkinson's disease, Alzheimer's disease, multi-infa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C50/28C07C46/00C07C46/10C07C46/04
CPCC07C46/00C07C46/04C07C46/10C07C50/28
Inventor 王金胡晓王文玲严燚宇汤磊
Owner YANGZHOU ZHONGHUI BIOTECH
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